Solid-phase synthesis of aryl-substituted thienoindolizines: sequential Pictet-Spengler, bromination and Suzuki cross-coupling reactions of thiophenes

Journal of Combinatorial Chemistry
Sebastian T Le QuementMorten Meldal

Abstract

The solid-phase synthesis of a range of novel heterocyclic scaffolds based on the thiophene ring system, including thienoindolizines and aryl-substituted thiophenes, is presented. Specifically, a sequential methodology for the decoration of thienoindolizine scaffolds has been developed. This method involves a highly efficient and diastereoselective intramolecular Pictet-Spengler reaction, a quantitative and regioselective bromination of the thiophene ring, and a final Suzuki cross-coupling with an arylboronic acid. Crude products were generally obtained in high purities (>90%). In addition, an investigation on the acidic and electronic effects governing the rate of the Pictet-Spengler reactions was performed. Finally, a range of substituted thiophenes was attached to solid supports and subjected to the regioselective bromination and Suzuki cross-coupling reactions, thus providing substituted thiophenes with high purities of crude products.

References

Feb 5, 2003·Bioorganic & Medicinal Chemistry Letters·Monica BubenikLaval Chan
May 2, 2003·Journal of Medicinal Chemistry·Henning LütjensPeter J Scammells
Feb 26, 2004·Bioorganic & Medicinal Chemistry·P Rajender KumarPragathi Hegde
Mar 5, 2004·Journal of Medicinal Chemistry·Vincent LisowskiSylvain Rault
Mar 5, 2004·Journal of Medicinal Chemistry·Yiqian WanMathias Alterman
May 22, 2004·The Journal of Organic Chemistry·Thomas E Nielsen, Morten Meldal
Sep 11, 2004·Bioorganic & Medicinal Chemistry·Braj Bhushan LohrayPurvi Pandya
Jul 12, 2005·Journal of Combinatorial Chemistry·Thomas E Nielsen, Morten Meldal
Nov 13, 2007·Journal of Combinatorial Chemistry·Sebastian T Le QuementMorten Meldal

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Citations

Sep 13, 2011·ACS Combinatorial Science·Sebastian T Le QuementThomas E Nielsen
Aug 11, 2011·Angewandte Chemie·Joachim StöckigtHerbert Waldmann
Mar 13, 2010·Biopolymers·Sebastian T Le QuementThomas E Nielsen
Feb 27, 2015·Bioorganic & Medicinal Chemistry·Mette R HansenThomas E Nielsen
Oct 22, 2019·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Sambasivarao Kotha, Milind Meshram
Jan 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andrea CalcaterraFrancesca Ghirga
Mar 16, 2013·Chemical Communications : Chem Comm·Huawen HuangHuanfeng Jiang

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